Synthesis and characterization of a new thermosensitive MOF@Lipid nanocarrier system for MRI assisted targeted tumor therapy

该研究项目的目的是合成和表征一种新的纳米载体系统，该系统在磁共振成像（MRI）的辅助下适合作为人类靶向肿瘤治疗的治疗诊断递送系统。为此，将研究一种新的、高度通用的多孔材料类别：金属有机框架（MOFs）。关键思想是通过创建功能化的MOF@Lipid系统来协同地联合收割机组合MOF纳米颗粒和热敏脂质体（TSL）的特征。TSL也是纳米载体，目前正在临床上进行测试，并正在不断开发中。这种组合的M0F@TSL系统相对于单独的TSL的主要优点是包封更宽范围的生物活性剂如细胞生长抑制剂和/或造影剂的选择。此外，与相同尺寸的脂质体相比，MOF的高度多孔的核为治疗剂或诊断剂提供了更高的负载能力。治疗概念基于热敏性MOF纳米载体的产生，其允许药物和MRI造影剂的非共价负载，以及另外通过局部热疗法在靶体积中控制释放药剂。肿瘤中的积聚和造影剂的释放可以通过MR成像来验证。因此，MRI可以允许控制热疗，以提供药物释放的间接证据，或者甚至可以允许定量药物释放（化学剂量测定法）。优化的非共价药物载体M0F@TSL系统的另一个益处是其用作其他治疗应用的平台的特征。

The aim of the research project is the synthesis and characterization of a new nanocarrier system that, assisted by magnetic resonance imaging (MRI) is suitable as a theranostic delivery system for targeted tumor therapy in humans. For that purpose a new, highly versatile and porous material class: metal-organic frameworks (MOFs) will be investigated. The key idea is to synergistically combine the features of MOF nanoparticles and thermosensitive liposomes (TSL) by creating functionalized MOF@Lipid systems. TSL are also nanocarriers, which are currently being tested clinically and which are under constant development. The major advantage of such a combined MOF@TSL system over TSL alone is the option to encapsulate a wider range of biologically active agents such as cytostatic and/or contrast agents. Additionally, the highly porous core of the MOF offers a higher loading capacity for therapeutical or diagnostic agents when compared to liposomes of the same size. The therapeutic concept is based on the creation of thermosensitive MOF nanocarriers that allow non-covalent loading of drugs and MRI contrast agents and additionally the controlled release of the agents in the target volume by local thermotherapy. The accumulation in the tumor and release of the contrast agent can be verified by MR imaging. Thus, MRI may allow to control the thermotherapy, to provide an indirect proof of drug release or even may allow quantification of drug release (chemodosimetry). Another benefit of an optimized non-covalent drug carrier MOF@TSL system is its feature to serve as a platform for other therapeutical applications.